"Duality In the Human Genome" Response
Article Summary: The main idea highlighted within this article (called Duality In the Human Genome by Max-Planck-Gesellschaft) is that the current methods of genetic analyses are flawed in the sense that they don’t take into account the dual nature of the human genome. Every human has two sets of genetic material, one set from their maternal line and one set from their paternal line. The study covered within this article analyzes both sets of the human genetic material and makes some interesting discoveries about how we should be thinking about the human genome. Flaw In the System: Current genetic analysis methods fail to take into account the fact that all humans have two different sets of genetic material. Most current methods simply analyze a mixed product of the genomes of humans. This study promotes the alteration of current trains of thought about human genes and genomes. Another common notion that this study refutes is the idea that individual mutations within the genetic makeup of human genomes are a random phenomenon. In order to prove this, both chromosomes need to have their unique set of genetic material analyzed for variation within the combination of genes within them. Study Overview: A team of scientists at the Max Planck Institute for Molecular Genetics in Berlin conducted a study in which they analyzed the genetic makeup of many people by decoding the genetic information on both sets of chromosomes separately. The maternal and paternal genomes of 14 people were decoded and then there was further supplementation for the final analyses in the form of genome data gathered from 372 Europeans from the 1000 Genomes Project conducted in 2001. Results: The two main results of this study were that there exists millions of different gene forms within the human genome and that the mutations within human genomes are not random. In regards to the existence of many different gene forms, the following data was gathered: * There were about 250 different forms of each gene within the human genomes. * There were about 4 million different gene forms within the genome sequenced (about 400). * More than 85% of genes don’t have a predominant form in which they exist, which means that one form doesn’t exist more than 50% of the time. * Over ½ (9,000-17,500) of the genes in any one person are unique to that specific person. * 96% of genes have at least 5-20 different protein forms that they can produce. In regards to the observation that random mutations do not occur within the human genome, the following data was gathered: * A 60:40 ratio of mutation types exists in all human genomes. ** 60% of mutations affect the same chromosome set (cis). ** 40% of mutations affect both the chromosome sets (trans). ** This ratio helps us understand gene variability and how it affects gene function. * Within a set of about 4,000 genes that are altered by mutations, the proteins created occur in predominantly 2 different forms. ** This duality helps control the immune system, gene activity, and signal transmission between cells. ** It also allows for better adaptation by the gene because it can make the appropriate protein form depending on the environmental circumstances. ** Of these 4,000 “dual genes,” many of them are disease-associated genes, which makes sense because when they fail to function properly they cause the disease states. Takeaway: The big key takeaway from this study is that the current manner in which genetic analysis is being carried out may in fact be flawed due to the failure of taking into account the two different sets of genetic material that exist within the two different chromosomes of an individual's genome. Individualized gene therapies are even more difficult as a result of this study because they need to take into account the “dual nature” within the human genome. Also, current genetic analyses measure the risk of a disease by taking into account the presence or absence of gene, but the location of a mutation within certain genes (mutation distribution) needs to be taken into account as well. This study challenges the interpretation of current genetic analyses and how they can be used to predict certain disease outcomes. Resources: # Max-Planck-Gesellschaft. "Duality in the human genome." ScienceDaily. ScienceDaily, 1 December 2014. # Margret R. Hoehe, George M. Church, Hans Lehrach, Thomas Kroslak, Stefanie Palczewski, Katja Nowick, Sabrina Schulz, Eun-Kyung Suk, Thomas Huebsch. Multiple Haplotype-Resolved Genomes Reveal Population Patterns of Gene and Protein Diplotypes. Nature Communications, 2014; 5: 5569 DOI:10.1038/ncomms6569